Atherosclerosis is the root cause behind most heart attacks and strokes, making it the number one cause of mortality and morbidity in the United States. Methods are needed that permit evaluation of atherosclerotic lesion composition and morphology in vivo. Such methods would enable medical professionals to base treatment decisions on accurate risk assessments, support pre-interventional planning, and facilitate pharmaceutical trials that evaluate drug effects directly on the lesions. The goal of this proposal is to help meet these needs by performing the clinical trials necessary to obtain FDA approval to market our Quantitative Vascular Analysis System (QVAS) for two uses. The first use will employ the unique plaque lesion characterization methods of QVAS to generate a comprehensive risk score indicating whether a patient with carotid stenosis would benefit from surgical intervention such as carotid endarterectomy (CEA) or stenting. This use would allow the clinical guidelines for such interventions developed by the American Heart Association, which currently employ a single quantitative measure (carotid stenosis), to be updated with a more effective predictor of treatment outcome. For the second use, QVAS will generate a 3D visualization of the involved section of the carotid artery for use in pre-intervention treatment planning. This visualization would allow a surgeon to examine the full spatial extent and distribution of the different plaque components in order to select the intervention most likely to produce a positive outcome. We will also bring QVAS into compliance with the DICOM image exchange standard and the Clinical Data Interchange (CDISC) standard, as well as use the results and feedback from the trials to improve the reliability and effectiveness of QVAS. In order to meet this goal, we will continue the strategic relationship with the University of Washington's Vascular Imaging Lab (VIL) that has successfully developed the QVAS product under Phase I and Phase II SBIR grants. The VIL will develop a standardized training program, train the participating clinical sites, and act as the overall clinical data manager.